CAPN3 mutations in patients with idiopathic eosinophilic myositis
CAPN3 mutations in patients with idiopathic eosinophilic myositis
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DOI：
10.1002/ana.20833
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发表时间：
2006-06-01
影响因子：
11.2
通讯作者：
Levy, Nicolas
中科院分区：
文献类型：
--
作者：
Krahn, Martin;Lopez de Munain, Adolfo;Levy, Nicolas
目的：嗜酸性肌炎（EM）是一种罕见的病理实体，其特征是骨骼肌嗜酸性粒细胞浸润，通常与寄生虫感染、全身性疾病或药物或 L-色氨酸的摄入有关。排除此类原因即可定义特发性 EM 的范围。基于对一名受影响患者进行的蛋白质分析，我们确定了编码 calpain-3 (CAPN3) 的基因作为特发性 EM 子集的候选基因。方法：我们使用 DHPLC 和直接测序在六名不相关的患者中筛选 CAPN3 突变，这些患者在肌肉活检样本的组织学检查后诊断为 EM，没有任何确定的致病因素。结果：我们在最初诊断为特发性 EM 的六名不相关患者中确定了 CAPN3 突变。 EM.解释：CAPN3 突变可导致 EM。因此，特发性 EM 的一个子集是由基因决定的，具有常染色体隐性遗传模式。患者出现的三联征似乎表明 CAPN3 突变：(I) 第一个十年出现 EM，(2) 血清肌酸磷酸激酶水平升高（孤立或几乎没有相应的无力），以及 (3) 不稳定的外周嗜酸性粒细胞增多。然而，EM 代表了与 CAPN3 突变相关的独特表型，或者更确切地说，必须进一步评估 LGMD2A 的早期组织病理学图像。我们的研究结果应该对进一步研究 calpain-3 在骨骼肌中的作用感兴趣。此外，特发性 EM 患者应接受 calpain-3 蛋白分析，并考虑进行 CAPN3 基因的后续分子分析。
Objective: Eosinophilic myositis (EM) constitutes a rare pathological entity characterized by eosinophilic infiltration of skeletal muscles, usually associated with parasite infections, systemic disorders, or the intake of drugs or L-tryptophan. The exclusion of such causes defines the spectrum of idiopathic EM. Based on a protein analysis performed in one affected patient, we identified the gene encoding calpain-3, CAPN3, as a candidate for a subset of idiopathic EM.Methods: We screened CAPN3 for mutations using DHPLC and direct sequencing in six unrelated patients, recruited for EM diagnosed after histological examination of muscle biopsy samples, without any identified causative factor.Results: We identified CAPN3 mutations in the six unrelated patients originally diagnosed with idiopathic EM.Interpretation: Mutations in CAPN3 can cause EM. Thus, a subset of idiopathic EM is genetically determined, with an autosomal recessive mode of inheritance. Patients presented with a triad that appears to be indicative of CAPN3 mutations: (I) EM in the first decade, (2) elevated serum creatine phosphokinase levels (isolated or with little corresponding weakness), and (3) inconstant peripheral hypereosinophilia. However, that EM represents a distinct phenotype associated to CAPN3 mutations or, rather, an early histopathological picture of LGMD2A must be further evaluated. Our findings should be of interest toward further investigating the role of calpain-3 in skeletal muscle. Furthermore, patients with idiopathic EM should undergo calpain-3 protein analysis and be considered for subsequent molecular analysis of the CAPN3 gene.